RGD Reference Report - Comparison between single and combined treatment with candesartan and pioglitazone following transient focal ischemia in rat brain. - Rat Genome Database

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Comparison between single and combined treatment with candesartan and pioglitazone following transient focal ischemia in rat brain.

Authors: Schmerbach, K  Schefe, JH  Krikov, M  Muller, S  Villringer, A  Kintscher, U  Unger, T  Thoene-Reineke, C 
Citation: Schmerbach K, etal., Brain Res. 2008 May 7;1208:225-33. Epub 2008 Mar 4.
RGD ID: 2301892
Pubmed: PMID:18378216   (View Abstract at PubMed)
DOI: DOI:10.1016/j.brainres.2008.02.032   (Journal Full-text)

Angiotensin AT1 receptor blockers (ARBs) and thiazolidinediones (TZDs) have become well established drugs for the treatment of major risk factors of stroke. Since several studies provided evidence that ARBs and TZDs also have additional anti-inflammatory effects, we hypothesized that a combined treatment with the ARB, candesartan, and the TZD, pioglitazone, ameliorates ischemia-induced brain injury and inflammation by synergistic anti-inflammatory actions. Normotensive Wistar rats were pre-treated for 5 days with vehicle (0.9% NaCl), 0.2 mg/kg/day candesartan (s.c.), and/or 2 and/or 20 mg/kg/day pioglitazone (p.o.), respectively and underwent 90 min of middle cerebral artery occlusion (MCAO) with successive reperfusion. Neurological deficits and infarct size were determined 24 h and 48 h after MCAO, respectively, followed by tissue sampling. Animals treated with candesartan, pioglitazone, and the combination of candesartan and pioglitazone had reduced neurological deficits 24 h and 48 h after MCAO, respectively (P<0.05-0.01). Infarct size was reduced by treatment of candesartan, pioglitazone, and their respective combination (each P<0.05) 48 h after stroke compared to vehicle. Treatment with candesartan, pioglitazone, and their combination resulted in significantly reduced mRNA expression of the inflammatory markers CXCL1 and TNFalpha in vivo (P<0.01). The combination of candesartan plus pioglitazone is equally effective compared to their single applications concerning neuroprotection and attenuation of inflammation after MCAO. Therefore, we conclude that a direct synergistic neuroprotective action of parallel ARB and TZD treatment is unlikely.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
transient cerebral ischemia  ISOPparg (Rattus norvegicus)2301892; 2301892 RGD 
transient cerebral ischemia  IMP 2301892 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Pparg  (peroxisome proliferator-activated receptor gamma)

Genes (Mus musculus)
Pparg  (peroxisome proliferator activated receptor gamma)

Genes (Homo sapiens)
PPARG  (peroxisome proliferator activated receptor gamma)


Additional Information